Cautionary notes on the COVID-19 re-infection study
Authors: Zhi Qu
Journal: The Lancet (2023)

The COVID-19 Forecasting Team's systematic review and meta-analysis indicated a high protective effect of past SARS-CoV-2 infection against re-infection with pre-omicron variants.1COVID-19 Forecasting TeamPast SARS-CoV-2 infection protection against re-infection: a systematic review and meta-analysis.Lancet. 2023; 401: 833-842Summary Full Text Full Text PDF PubMed Scopus (151) Google Scholar As an interested reader of this study, I suggest a more cautious interpretation of the current findings due to potential sources of bias in the risk of re-infection assessment. First, individuals who have recovered from COVID-19 might engage in high-risk activities due to their belief in natural immunity.2Mori T Nagata T Ikegami K et al.Effect of COVID-19 infection related experiences on social behaviors when a state of emergency is declared: a cohort study.BMC Public Health. 2022; 222445Crossref Scopus (1) Google Scholar, 3Hansen CH Michlmayr D Gubbels SM Mølbak K Ethelberg S Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study.Lancet. 2021; 397: 1204-1212Summary Full Text Full Text PDF PubMed Scopus (438) Google Scholar This increased risk-taking behaviour makes previously infected people more susceptible to a subsequent infection and their lower likelihood to test again could further lead to an overestimation of the protective effect of infection.3Hansen CH Michlmayr D Gubbels SM Mølbak K Ethelberg S Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study.Lancet. 2021; 397: 1204-1212Summary Full Text Full Text PDF PubMed Scopus (438) Google Scholar Second, policy changes related to the COVID-19 pandemic can influence infection risk at the population level, which varies between countries. Rapid relaxation of COVID-19 restrictions could increase the risk of re-infection and therefore underestimate the protective effect of previous infection when compared with countries with slower relaxation measures. This difference in the pace of relaxation of restrictions could potentially lead to biased estimation of the effect of previous infection in different directions.4Talic S Shah S Wild H et al.Effectiveness of public health measures in reducing the incidence of COVID-19, SARS-CoV-2 transmission, and COVID-19 mortality: systematic review and meta-analysis.BMJ. 2021; 375e068302PubMed Google Scholar Finally, it is important to consider demographic differences among included studies, such as age distribution (eg, Qatar has a substantial younger population5Abu-Raddad LJ Chemaitelly H Ayoub HH et al.Characterizing the Qatar advanced-phase SARS-CoV-2 epidemic.Sci Rep. 2021; 11: 1-15Crossref Scopus (68) Google Scholar), when generalising the findings. As a study that integrates available evidence, it is worth addressing these potential sources of bias and their impact on the current analyses. I declare no competing interests. Past SARS-CoV-2 infection protection against re-infection: a systematic review and meta-analysisProtection from past infection against re-infection from pre-omicron variants was very high and remained high even after 40 weeks. Protection was substantially lower for the omicron BA.1 variant and declined more rapidly over time than protection against previous variants. Protection from severe disease was high for all variants. The immunity conferred by past infection should be weighed alongside protection from vaccination when assessing future disease burden from COVID-19, providing guidance on when individuals should be vaccinated, and designing policies that mandate vaccination for workers or restrict access, on the basis of immune status, to settings where the risk of transmission is high, such as travel and high-occupancy indoor settings. Full-Text PDF Open Access